Activation of protein kinase B/Akt by alpha1-adrenoceptors in the human prostate.

Frank Strittmatter, Sebastian Walther, Alexander Roosen, Beata Rutz, Boris Schlenker, Sebastian Limmer, Raphaela Waidelich, Christian G Stief, Christian Gratzke, Martin Hennenberg

Department of Urology, Ludwig-Maximilians University, Munich, Germany.

Life sciences 2012 Mar 10

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Besides their role in contraction, α1-adrenoceptors may be involved in prostate hyperplasia. This would require receptor signaling by growth-promoting pathways. Akt (syn. Protein kinase B) is an important regulator of growth and differentiation. Objective: To investigate whether α1-adrenoceptors in the human prostate activate Akt. Prostate tissue was obtained from patients undergoing radical prostatectomy. Akt expression was investigated by RT-PCR, Western blot, and immunohistochemistry. Akt activation by noradrenaline (30 μM) and phenylephrine (10 μM) was assessed by Western blot analyses with a phospho-specific antibody. The effects of the Akt inhibitors FPA-124 and 10-DEBC on phenylephrine-, noradrenaline- and electric field stimulation- (EFS-) induced contraction were studied in myographic measurements. mRNA of all three Akt isoforms (Akt1, Akt2, Akt3) was detected by RT-PCR in all prostate samples (n=6 patients). Protein expression was confirmed by Western blot analysis (n=8 patients). Immunohistochemical staining for Akt revealed strong immunoreactivity in prostate smooth muscle cells (n=5 patients). Stimulation of prostate tissues with noradrenaline (30 μM, n=8 patients) or phenylephrine (10 μM, n=7 patients) caused significant Akt phosphorylation at serine-473, indicating activation of Akt. FPA124 and 10-DEBC were without effects on noradrenaline-, phenylephrine-, or EFS-induced contraction of prostate strips. Prostate α1-adrenoceptors activate Akt. Consequently, Akt is a target of α1-blocker therapy, which has been unknown to date. Our findings point to functions of prostate α1-adrenoceptors besides contraction. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Frank Strittmatter, Sebastian Walther, Alexander Roosen, Beata Rutz, Boris Schlenker, Sebastian Limmer, Raphaela Waidelich, Christian G Stief, Christian Gratzke, Martin Hennenberg. Activation of protein kinase B/Akt by alpha1-adrenoceptors in the human prostate. Life sciences. 2012 Mar 10;90(11-12):446-53